Efficacy and Safety of a Single Low-dose Primaquine for the Clearance of Gametocytes

Sponsor

Muhimbili University of Health and Allied Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT02090036

Collaborator

Karolinska Institutet (Other)

220

Enrollment

Location

Arms

Duration (Months)

54.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess efficacy and safety of a single low-dose Primaquine added to standard artemether/lumefantrine treatment for the clearance of Plasmodium falciparum gametocytes among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum	Drug: Primaquine (For artemether-lumefantrine+primaquine arm) Drug: Placebo (For artemether-lumefantrine arm)	Phase 4

Detailed Description

The current gained successes in malaria control are accredited partly to the availability of efficacious and fast acting artemisinins which are also potent against P. falciparum young gametocytes. Nonetheless, mature gametocytes may persist after treatment, contributing to malaria transmission. Conversely, artemisinin resistance is confirmed in South-east Asia, and it may spread to Africa. New control tools have to be integrated to sustain the gained successes, further reduce transmission and curb the spread of resistance.

Primaquine has strong gametocytocidal effect against mature gametocytes and when added to schizonticidal drugs such as artemether-lumefantrine (AL), it rapidly shorten gametocytes carriage duration, halting disease transmission. Nonetheless, its wide scale use has been hampered by a dose-dependent acute hemolytic anemia it causes in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. Conversely, Artemisinins potentiate primaquine activities, thus a low dose of primaquine would be able to clear falciparum gametocytes.

The World Health Organization recommends addition of 0.25 mg/kg single-dose primaquine to Artemisinin based combination therapies in malaria endemic areas including Africa without testing for G6PD status. Nonetheless, the recommendation, relies on historical data from South-East Asia and among African Americans in the United States. Therefore, this study plans to assess safety and efficacy of 0.25 mg/kg single-dose primaquine added to a standard AL treatment against P. falciparum gametocytes clearance among patients with uncomplicated malaria aged 1 year and above regardless of their G6PD status..

Study Design

Study Type:

Interventional

Actual Enrollment :

220 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Efficacy and Safety of a Single Low-dose Primaquine Added to Standard Artemether-lumefantrine Treatment for the Clearance of Plasmodium Falciparum Gametocytes.

Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: artemether-lumefantrine+placebo In the artemether-lumefantrine arm, the first dose of artemether-lumefantrine will be administered concomitantly with a single-dose placebo. A volume of normal saline will be measured based on weight bands and then will be given to patients.	Drug: Placebo (For artemether-lumefantrine arm) Volume of normal saline mixed with coloured fruit juice measured based on weight bands will be given orally concomitantly with first dose of artemether-lumefantrine.
Experimental: artemether-lumefantrine+primaquine All the recruited patients will be treated with a six doses, 3 days artemether-lumefantrine treatment regimen. However, patients randomized to the artemether-lumefantrine+primaquine arm will be given 0.25 mg/kg single-dose primaquine concomitantly with artemether-lumefantrine first dose.	Drug: Primaquine (For artemether-lumefantrine+primaquine arm) A 0.25 mg/kg single-dose primaquine will be administered concomitantly with the first dose of artemether-lumefantrine in all patients randomized into the artemether-lumefantrine+primaquine arm.

Arm

Intervention/Treatment

Active Comparator: artemether-lumefantrine+placebo

In the artemether-lumefantrine arm, the first dose of artemether-lumefantrine will be administered concomitantly with a single-dose placebo. A volume of normal saline will be measured based on weight bands and then will be given to patients.

Drug: Placebo (For artemether-lumefantrine arm)

Volume of normal saline mixed with coloured fruit juice measured based on weight bands will be given orally concomitantly with first dose of artemether-lumefantrine.

Experimental: artemether-lumefantrine+primaquine

All the recruited patients will be treated with a six doses, 3 days artemether-lumefantrine treatment regimen. However, patients randomized to the artemether-lumefantrine+primaquine arm will be given 0.25 mg/kg single-dose primaquine concomitantly with artemether-lumefantrine first dose.

Drug: Primaquine (For artemether-lumefantrine+primaquine arm)

A 0.25 mg/kg single-dose primaquine will be administered concomitantly with the first dose of artemether-lumefantrine in all patients randomized into the artemether-lumefantrine+primaquine arm.

Outcome Measures

Primary Outcome Measures

Number of days per treatment arm for gametocytes to become undetectable using Quantitative nucleic acid sequence based assay (QT-NASBA). [14 days]

Secondary Outcome Measures

Mean maximal fall in hemoglobin (g/dl) from enrolment to day 28 of follow-up defined as mean greatest negative difference in hemoglobin per treatment arm. [28 days.]

Other Outcome Measures

Proportion of patients with urine color change score ≥ 5 using Hillmen Urine Colour Chart, per treatment arm. [28 days.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age of 1 year and above and neither pregnant nor breast feeding.
Weight over 10 kg.
Body temperature ≥37.5°C) or history of fever in the last 24 hours.
1. falciparum mono-infection.

Exclusion Criteria:

Evidence of severe illness malaria or danger signs.
Known allergy to study medications.
Hemoglobin <8 g/dl.
Antimalarials taken within last 2 weeks.
Blood transfusion within last 90 days and evidence of recent use (within 14 days)of or will be taking other drugs known to cause hemolysis in G6PD deficient subjects.